Research

The A.I.M. Interview: Algae Genetic Engineer Dr. Stephen Mayfield

If moving genes around on a chromosome is your idea of a good time, meet Dr. Stephen Mayfield, Director of the San Diego Center for Algae Biotechnology. A PhD geneticist from UC Berkeley, Steve loves his work, sometimes to the distress of his family. “That’s what I really like to do—take genes, move them around, put them back in, and see what they do,” he says.

“I get excited when I see a new band on a gel and I’ve made a new protein. I can’t explain to you why. Early on my wife looked at that and said, ‘You’re excited about that? That’s really sad.’ And I said, ‘You don’t understand. There’s potential there!’ ”

But like I said, Steve loves his work, and sees great potential in algae and the projects he has been able to work on over the past 25 years. One of them, in fact, was Sapphire Energy, which began in his lab. But we’ll come back to that.

Formerly a Professor of Cell Biology, and Associate Dean of the graduate school at The Scripps Research Institute (TSRI), in San Diego, Steve is now the John Dove Isaacs Professor of Natural Philosophy at the University of California San Diego, where he maintains his lab. In that capacity, much of his current work revolves around the San Diego Center for Algae Biotechnology (SD-CAB), which he co-founded three years ago.

“The original idea was that the academic and commercial guys here in San Diego working on different aspects of algae should get together,” Steve says. “I was, and am, very committed to this idea that we need to get technologies out of academic research institutions and into commercialization as quickly as we can. That is something that is good for the country, good for science, good for the commercial guys and it’s good for the academic guys, too.

“So, I roped in Greg Mitchell, who’s at Scripps Institution of Oceanography, and Steve Kay, who’s the Dean of Biological Sciences here at UCSD. The three of us got together and decided it was time to pull all of the academic guys together and set up this center so that we could nucleate, more or less, the participation of academics together with commercial guys in what we saw as the newly developing field of algae biotechnology.”

They called it the Center for Algae Biotechnology, rather than the Center for Algae Biofuels, partly because Steve’s background was in making therapeutic proteins, as he continues to do, and also because they all believed that it’s not just bioenergy that’s important. “Certainly that is the driving force right now for most people,” he says. “But there are so many other things that will come out of algal biotechnology—neutraceuticals, biopolymers, animal feed, therapeutic proteins, industrial enzymes, all of these things can be enabled by the technology we’re working on, and all of these things should and will be enabled.

“In fact many of them will have commercial success before we have commercial success in bioenergy,” he says. “The reason is obvious. Therapeutic proteins can sell for thousands of dollars a gram—millions of dollars a kilogram. Those numbers simply drive the commercialization aspect of the technologies much quicker than fuel can. And we all complain about gas at $4.00 a gallon! Those economics are going to take a while before we get to them.”

As the academic collective began to pursue commercial partners, they connected with companies including Neste Oil, Chevron Oil, Sempra Energy, Kent Bioenergy, Life Technologies, and Praxair, not all specifically interested in the bioenergy component, but all interested in some aspect of algal biotechnology.

A 40-acre algae farm just east of the Salton Sea in Imperial Valley near Niland. SD-CAB scientists will demonstrate the feasibility of growing algae for biofuels on a large scale here. These mid-sized “raceway” ponds circulate 20,000 to 37,000 gallons of growing algae. Credit: Jim Demattia

How do SD-CAB’s academic and commercial partners work together?

I think there are two layers to this. The first one consists of companies who fully engage. These are companies like Sapphire Energy, General Atomics, Sempra Energy and Life Technologies, who are doing specific collaborative projects with us or with one of the faculty in SD-CAB. These guys come to the table, they bring their scientists, they meet with us, and we work together on projects.

And then there is a second tier of companies that just wants a seat at the table. These might be companies like Chevron, Nike, companies that have an interest in green technologies, that certainly want to see them be successful, but don’t have a specific project today that they want to work with us on. But, they want to be part of the discussion, and they want to make sure they are well informed about how the technology is moving forward. They want to see how it can impact their businesses and ultimately how can they participate.

As an example of the first type, I’m going up to Life Technologies on Monday to give them a general science seminar on what it is we can do in algae, and to start to talk to them about how Life Technologies can help enable algae biotechnology, by selling all of the vectors, media, and reagents for algae the way they do with yeast and mammalian cells now. They want to do that same thing for algae. So I’m happy to participate on this front. Yes, we’ll collaborate with you to get these vectors transferred over so you can sell them in your catalog. I think that’s a great idea.

How far down the road is this?

We have a couple of therapeutic proteins that we will put into animals this fall with the hopes that if we are successful in that, at some time in 2011 we may start clinical trials.

As far as the SD-CAB’s relationship with the DOE and the $9 million funding announced earlier this year, what exactly is that for?

We put in a proposal to DOE in competition with many other groups including the Los Alamos group (NAABB). And it was pretty much the same for all of these consortia. We had to answer the DOE’s 10 points, everything from discovery of new species to modification of those, to fuel extraction, to dewatering… We all put in pretty similar proposals.

The Los Alamos proposal was chosen, but it only covered half of the topics. So then DOE did a very smart thing and actually went back and looked at the other proposals again and said, “We’re going to fund mainly the Los Alamos group, but there are some gaps and we’re going to fill these by going back to those other proposals which had very good reviews and cherry pick from them.”

So, what gap is SD-CAB covering?

We are covering three aspects. One is crop protection, one of the biggest problems out there. Second is nutrient utilization and recycling, and our third is genetic tools.

Any other big SD-CAB projects on the table?

We just received a $4 million grant, over two years, from the state of California to develop a bioenergy training program. That grant is actually going to SD-CAB, plus CleanTECH San Diego, plus BioCom San Diego, plus San Diego Workforce Partnerships. Three of those are dot orgs here in San Diego, which are set up to do bioenergy, cleantech and commercial sector interactions and connectivity. The part that we/SD-CAB brings to that is we’ll generate course content and set up the certificate training programs.

We’re going to develop four certificate programs, one in biomass production, one in bioenergy technician, one in crop management and the algal pathogenesis, and the fourth one is in advanced science. Each one will have about 3-5 courses in them. Some of those courses already exist, and some we’re going to develop new. The new ones will be developed by faculty within SD-CAB. There are ten faculty participating in that, including me.

How will these courses eventually be offered?

Through three different groups: UC San Diego’s extension program, San Diego State University, and MiraCosta Community College. That represents programs in a two-year community college, a California state college and a California university. At first we will teach those classes and have the certificate programs here in San Diego. But the way we’re setting up the whole system is to make this completely exportable. So if a group in New Mexico, for example, looked at this and says, “Oh, that looks like a good program. We’d like to bring it down here,” we are going to make these programs available on a web base so they can do that.

Chlamydomonas

What most excites you about the potential of algae in the future of our civilization?

Well, let me turn that question on its head. What are my biggest concerns when I look at the bioenergy sector? It’s that we have managed to burn through—in a hundred years—half of the entire civilization’s allocation of fossil fuel. This is a few hundred million years of accumulated energy in the form of petroleum, coal and natural gas. And we are going to be done with the stuff in less than another hundred years.

Our population is growing and significant portions of that growth—China and India—have looked at us and decided that they like the way America runs. They want to be like us. And you know, the US is 5% of the world’s population and we use 25% of the world’s energy. If half of the world’s population—China and India and other developing countries—decide they want to consume energy at the same rate we do…well, something’s gotta give.

Either our standard of living is going to hugely drop as theirs comes up, or we are going to have to find new alternatives. What makes me the most nervous, what I lose sleep over, is can we really pull this off? Can we really as a society, number one, become much more efficient in the way we use energy, and two, develop the alternative sources—and algae’s got enormous potential for this. But can we really pull this off? Can algae, and every other alternative, wind, solar, cellulosic ethanol, can we really get those things to replace the hydrocarbons that we’ve depleted?

So, are you 90% sure we can? Are you 30%? What’s your level of confidence?

I’m a hundred percent certain we can replace some of them. I’m less than 5% certain we can replace all of them. What my best guess is, and what I’m making slides of to talk about at the ABO meeting in a couple of weeks, is that what is going to happen in the next ten to twenty year time frame is the cost of fossil fuel is going to go through the roof, and that’s not necessarily a bad thing.

When we get up to $250 to $300 dollars a barrel, then fuel has a value which is at least getting close to its true value. Right now we treat it like we have an endless supply and we’re just going to be able to burn it forever, and that’s just crazy. This is a drunken sailor spending money in a bar, the way we’ve been burning through our energy reserves.

And as the price goes up people will start to conserve it. They’ll start to realize that this stuff is really valuable; we shouldn’t just be pissing it away at the rate we are now. So we are going to become much more efficient and as we become more efficient we are going to extend the life of the hydrocarbons we have. And that will give us an opportunity to start to replace those with alternative sources—from algae, from cellulose, from wind, solar and all the other things.

As you talk about China and India’s desire for our lifestyle, the growth in fuel demand seems impossible to satisfy unless those countries grow at a much greener rate than we did here. Why would this be different? Wouldn’t they demand the latest fuel efficient technologies?

That hasn’t happened yet. I was just in Beijing last week, and what’s going on now is that the streets are clogged, I mean clogged with brand new Jettas and BMWs. It’s unbelievable. They drive big cars like in America. These are not next generation fuel-efficient anything.

We’ve created a monster. We sold this American image that happiness is a big house in the suburbs next to a golf course and a big SUV in the driveway. That is the most alarming thing, that people just haven’t realized this yet.

I think that there is zero chance that the world is going to stop burning fossil fuels because of climate change. The Kyoto Agreement and any others we might put up. I hate to say it, but it’s a joke. The political will isn’t there. People don’t care. They think, does driving my car really change the weather? I don’t think so.

OK, another subject. You’ve worked with algae under the microscope for over 25 years. You’re pretty chummy with them at this point. What’s your favorite strain?

Chlamydomonas is the green algae that I work on, and that’s my favorite strain only because the genome is sequenced and we have at least a pretty good set of genetic tools for it.

What I love is anything I can do genetic manipulation to, and right now that’s Chlamy. But that’s a freshwater algae that doesn’t grow to very high density. So what we’re doing in my lab, and in a lot of other labs, too, we need to get molecular tools into marine strains so we can grow biofuels in salt water. And we need to get strains that grow to much higher density and produce more lipids, etc.

What other parameters are you looking to optimize in genetically engineering these strains?

Several years ago when people first looked at this, everyone thought the big catches were going to be, can we get a growth rate of 30 grams per meter squared per day, and could we get high lipid content. And actually those two things turned out to be pretty achievable. The much tougher thing has turned out to be (a) crop protection, and (b) can we do all the tricks that have been developed in modern agriculture, like ease of harvesting, ease of storage…can we do that to algae? Can we really domesticate it? And that’s not going to be any one big discovery, that’s going to be a hundred little discoveries all adding up.

You’ve said words to the effect of: if we are to solve the impending petroleum depletion with algal oil, we have no choice but to employee genetic engineering. Can you clarify that?

This is a really simple one. Start with the understanding that there are zero native strains currently being used in any industrial food application. None. Zero. Zip. Not corn, not chickens, not pigs, not wheat, not alfalfa, none of that. Every single one of them is genetically modified. Now, how do you get those genetic modifications? Well, traditionally we’ve done it by selection and breeding. You go out in the field and pick your best strain and then you either mutate it or you plant a whole bunch of it in a field and you continue to select those things. Look at what we managed to do to dogs. You know Chihuahuas and great Danes are the same species? We’ve simply genetically modified those to different extremes.

So, all organisms are genetically modified. Because the minute you’ve gone out to select a better strain, you’ve modified the genome.

Now, some people will try to separate themselves on this point, and for me it’s splitting hairs. Whether I take the gene out and know exactly what it is and put it back, or whether I don’t know what the gene is because I just selected it from a pool of things that look different, either one of those are genetic modifications. In one of them I know exactly what I did, and in the other one I don’t know what I did but I still got the right outcome.

We’re going to use both of those things for bioenergy, but both of those are a modification, and people who tell you it’s something different either don’t understand genetics and genomes and what we really mean by genetic modification, or they have another agenda. I do exactly the same thing that nature has done. In the end, if biofuels are going to be successful, they are going to use genetically modified organisms.

One company was on a webinar with us just the other day. They said, “We are not using genetically modified organisms, we’re using breeding and selection.”

Excuse me. Breeding and selection are genetic modifications! So either those guys don’t understand that they are modifying the genomes of these things, or they’re just saying what they think is politically correct. But these guys are smart. They know perfectly well that genomes are modified and that’s how they get things through selection. They just don’t want to use the words “genetic modification.”

I think we’ve done an enormous disservice to the world, as scientists, by allowing ignorance to dominate our conversations. Take the anti-GMO and self-proclaimed environmentalists that want to block any genetic modification to algae because of some imagined danger to the environment. We are destroying our environment at an alarming rate, whether that is deforestation, over fishing the oceans, strip mining, or our unabated dumping of pollutants into the air and oceans, these are real significant problems that we better face.

What do we do instead? We make up outlandish scenarios and then scream “these could destroy the earth!” Hey, look around. Weare destroying the earth! This is like insisting that the fire department come to a parking lot and analyze the fire danger, when the school and library down the street are burning to the ground.

So here is my idea: let’s be thoughtful and careful with what we do, but let’s not make up far fetch stories about monsters that don’t exist, and lets save our energy for the real things that are killing the planet right before our eyes.

That lie is exactly the same as people who tell you, “Don’t genetically modify my food.” All your food is genetically modified. Do you think you go out in the wild and find anything that looks like a corn plant? Have you ever seen anything in the wild that looks like a pig or a cow? Where did those come from? We bred those things! They vaguely look like wild hogs and like buffalo, but we modified them to be what we wanted them to be.

Part 2 – coming October 4th — more on genetic engineering of algae, and the birth of Sapphire Energy